QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 11, 2004, 24(32):7096-7109; doi:10.1523/JNEUROSCI.0780-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Scott, D. B. Articles by Ehlers, M. D. Search for Related Content PubMed PubMed Citation Articles by Scott, D. B. Articles by Ehlers, M. D.

 Previous Article  |  Next Article 

Cellular/Molecular
Endocytosis and Degradative Sorting of NMDA Receptors by Conserved Membrane-Proximal Signals

Derek B. Scott,^1,2 Ioannis Michailidis,⁶ Yuanyue Mu,³ Diomedes Logothetis,⁶ and Michael D. Ehlers^2,3,4,5

¹Program in Cell and Molecular Biology, Departments of ²Cell Biology, ³Neurobiology, ⁴Pharmacology and Cancer Biology, and ⁵Neuroproteomics Laboratory, Duke University Medical Center, Durham, North Carolina 27710, and ⁶Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029

Regulation of the abundance of NMDA receptors (NMDARs) at excitatory synapses is critical during changes in synaptic efficacy underlying learning and memory as well as during synapse formation throughout neural development. However, the molecular signals that govern NMDAR delivery, maintenance, and internalization remain unclear. In this study, we identify a conserved family of membrane-proximal endocytic signals, two within the NMDAR type 1 (NR1) subunit and one within the NR2A and NR2B subunits, necessary and sufficient to drive the internalization of NMDARs. These endocytic motifs reside in the region of NMDAR subunits immediately after the fourth membrane segment, a region implicated in use-dependent rundown and NMDA channel inactivation. Although endocytosis driven by the distal C-terminal domain of NR2B is followed by rapid recycling, internalization mediated by membrane-proximal motifs selectively targets receptors to late endosomes and accelerates degradation. These results define a novel conserved signature of NMDARs regulating internalization and postendocytic trafficking.

Key words: NMDA receptor; endocytosis; late endosome; excitatory synaptic transmission; synaptic plasticity; intracellular trafficking

---

Received March 3, 2004; revised June 17, 2004; accepted June 22, 2004.

This article has been cited by other articles:

				S. Zhang, L. Edelmann, J. Liu, J. E. Crandall, and M. A. Morabito Cdk5 Regulates the Phosphorylation of Tyrosine 1472 NR2B and the Surface Expression of NMDA Receptors J. Neurosci., January 9, 2008; 28(2): 415 - 424. [Abstract] [Full Text] [PDF]

				Z. Yi, R. S. Petralia, Z. Fu, C. C. Swanwick, Y.-X. Wang, K. Prybylowski, N. Sans, S. Vicini, and R. J. Wenthold The Role of the PDZ Protein GIPC in Regulating NMDA Receptor Trafficking J. Neurosci., October 24, 2007; 27(43): 11663 - 11675. [Abstract] [Full Text] [PDF]

				I. E. Michailidis, T. D. Helton, V. I. Petrou, T. Mirshahi, M. D. Ehlers, and D. E. Logothetis Phosphatidylinositol-4,5-Bisphosphate Regulates NMDA Receptor Activity through {alpha}-Actinin J. Neurosci., May 16, 2007; 27(20): 5523 - 5532. [Abstract] [Full Text] [PDF]

				K. M. Wiens, H. Lin, and D. Liao Rac1 Induces the Clustering of AMPA Receptors during Spinogenesis J. Neurosci., November 16, 2005; 25(46): 10627 - 10636. [Abstract] [Full Text] [PDF]

				Y. N. Dong, E. A. Waxman, and D. R. Lynch Interactions of Postsynaptic Density-95 and the NMDA Receptor 2 Subunit Control Calpain-Mediated Cleavage of the NMDA Receptor J. Neurosci., December 8, 2004; 24(49): 11035 - 11045. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help